DESCRIPTION: (Applicant's Abstract) Although craving for cocaine is identified as the key motivating factor perpetuating cocaine use and relapse, there is little understanding of the mechanisms underlying cocaine craving and the possible gender differences in cocaine craving responses. Drug abusers cite environmental stressors and psychological distress as among the most common triggers for relapse to drug use. While several animal studies have shown that acute stress increases self-administration of drugs, human laboratory studies demonstrating an association between acute stress and cocaine craving or cocaine relapse have been lacking. We have developed an effective personalized stress and drug cue imagery paradigm that reliably increases cocaine craving. In 60 cocaine abusing men and women we will test whether stress and drug cue imagery increase cocaine craving as compared to neutral imagery. Neurobiological correlates of stress-induced and drug-induced craving will be studied, and potential gender differences in these responses will be examined. We hypothesize the following: (1) Cocaine craving will increase with stress and drug cue imagery, and not during neutral imagery, (2) In contrast to neutral imagery, stress and drug cues will activate: (i) sympathetic responses as measured by increases in heart rate, skin conductance, finger temperature and blood pressure; (ii) the hypothalamic-pituitary-adrenal axis (HPA), as measured by plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin, and (iii) the dopaminergic system, as measured by homovanillic acid (HVA), (3) Women will exhibit greater stress-induced cocaine craving and stress reactivity than men, and (4) Increases in cortisol and HVA during stress imagery and drug cues imagery will be associated with stress-induced and drug cue-induced cocaine craving respectively. If our hypotheses are confirmed, the findings will provide (a) greater understanding of the mechanisms by which craving for cocaine is elicited, (b) new leads for the development of pharmacological interventions for cocaine abuse, and(c) modifications in state-of-the-art behavioral therapies for cocaine abuse.